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Sci Transl Med. 2014 Jul 30;6(247):247ra102. doi: 10.1126/scitranslmed.3008705.

New antigens for a multicomponent blood-stage malaria vaccine.

Author information

1
Pathogen Vector and Human Biology Department, Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast, P. O. Box 230, 80108 Kilifi, Kenya.
2
Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
3
Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK.
4
Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
5
Pathogen Vector and Human Biology Department, Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast, P. O. Box 230, 80108 Kilifi, Kenya. KMarsh@kemri-wellcome.org.

Abstract

An effective blood-stage vaccine against Plasmodium falciparum remains a research priority, but the number of antigens that have been translated into multicomponent vaccines for testing in clinical trials remains limited. Investigating the large number of potential targets found in the parasite proteome has been constrained by an inability to produce natively folded recombinant antigens for immunological studies. We overcame these constraints by generating a large library of biochemically active merozoite surface and secreted full-length ectodomain proteins. We then systematically examined the antibody reactivity against these proteins in a cohort of Kenyan children (n = 286) who were sampled at the start of a malaria transmission season and prospectively monitored for clinical episodes of malaria over the ensuing 6 months. We found that antibodies to previously untested or little-studied proteins had superior or equivalent potential protective efficacy to the handful of current leading malaria vaccine candidates. Moreover, cumulative responses to combinations comprising 5 of the 10 top-ranked antigens, including PF3D7_1136200, MSP2, RhopH3, P41, MSP11, MSP3, PF3D7_0606800, AMA1, Pf113, and MSRP1, were associated with 100% protection against clinical episodes of malaria. These data suggest not only that there are many more potential antigen candidates for the malaria vaccine development pipeline but also that effective vaccination may be achieved by combining a selection of these antigens.

PMID:
25080477
PMCID:
PMC4856877
DOI:
10.1126/scitranslmed.3008705
[Indexed for MEDLINE]
Free PMC Article

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